Plasma samples drawn simultaneously from portal and peripheral veins during laparotomy in nine patients revealed a portal immunoreactive glucagon (IRG) level of 182 +/- 32 (+/- SEM) and a peripheral level of 117 +/- 17 pg/ml with a portal to peripheral ratio of 1.58 +/- 0.11. On gel chromatographic studies of portal-peripheral sample pairs, the portal and peripheral levels of 3500 mol wt IRG were 108 +/- 36 and 44 +/- 15 pg/ml, respectively, with a substantially greater portal to peripheral ratio (2.77 +/- 0.53). There was, however, no transhepatic gradient for the void volume IRG fraction, the other major component of plasma IRG. These results suggest that the liver in man, analogous to that in lower mammals, is an important organ for glucagon extraction.